The proposed research deals with the structure, function and metabolism of nuclear proteins in intestinal epithelial cells - with particular attention to the characterization of two subsets of nuclear non-histone proteins which appear during carcinogenesis of the colon induced by 1,2-dimethylhydrazine (DMH). Similar proteins present in human colonic tumors will be isolated and used to develop antibodies to be employed in an immunofluorescent-staining procedure for the detection of such proteins in single cells of individuals at high risk for colon cancer. This may be useful in early diagnosis of malignant transformation. The tumor-associated proteins will also be characterized with respect to their DNA-binding properties and tested for their localization in "active" or "inactive" regions of the genome. Modification of nuclear proteins in intestinal epithelial cells by alkylating agents such as DMH gives rise to unknown derivatives of amino acids in proteins associated with DNA and HnRNA. These modified amino acids will be separated and identified. The mechanism by which protein carbamylating reagents, such as sodium cyanate, selectively block protein synthesis in tumor cells, including adenocarcinomas of the colon, will be investigated.